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New findings also show that the omega-3/omega-6 dietary ratio is key; Salmon’s orange pigment may make it a superior preventive partnerby Craig Weatherby

“Fish eyes” is not usually a complimentary term, but the findings of two new studies—both of which examined the effects of fish-rich diets on the risk of age-related macular degeneration—give the term a positive new spin.

Age-related macular degeneration (AMD) afflicts some 30 million people worldwide, and is a leading cause of vision loss in Americans 60 years of age and older. Accordingly, researchers have been eager to find out whether any foods possess AMD-preventive properties.

Until now, the leading contenders in the battle to prevent AMD have been two antioxidants called lutein (loo-teen) and zeaxanthin (zee-ah-zan-thin), found both in the retina of human eyes and in broccoli, corn, spinach, kale, chard, and certain other yellow-green vegetables. (See our sidebar—"How spinach and company protect eyes"—below.)

And judging by the findings of two new studies in this month’s edition of the Archives of Opthalmology (Chua B 2006 and Seddon JM 2006), it’s looking even more likely that, compared with lutein and zeaxanthin, fish will become an equal—or greater—ally in the battle to decelerate the aging process in our eyes.

The hypothesis that motivated the researchers to conduct the newly published studies is simple and plausible. Every day, cells in the retina and other eye tissues undergo attack from unstable molecules called oxygen free radicals, which are generated when sunlight hits any tissue in the body.

The resulting “oxidative stress” on cells in the eye incites an inflammatory response by the body that can increase and continue the damage. Omega-3s help protect eye cells both because they are essential constituents of cell membranes, needed to keep cells functioning optimally, and because their anti-inflammatory properties probably help dampen free-radical-incited inflammation.

The Australian “Blue Mountains” eye studyResearchers from the several Australian universities and research centers analyzed data collected from 2,335 volunteers who’d participated in the Blue Mountains Eye Study. The study ran from 1992 through 1994, and participants’ eyes were examined at the end of the five-year study.

Cases of AMD fall into “early” or “late” categories: terms that reflect their stage in the progression of the disease. These terms correspond, roughly, to the “dry” and “wet” forms of the disease (see “What is AMD” below).

The results of the Blue Mountains study showed different degrees of risk reduction for each stage.

Fish Consumption

Risk of Early AMD

Risk of Late AMD

1 meal or more per week

42% lower

56% lower

3 meals or more per week

38% lower

75% lower

As the table shows, the volunteers who enjoyed fish three or more times a week experienced an average 38 percent reduction in their risk of “early” AMD compared to people who ate fish only once a month, while those who ate fish three or more times a week enjoyed a truly impressive 75 percent reduction in risk.

Even those who reported eating fish just once a week cut their risk of developing AMD by 42 percent (early AMD) to 56 percent (late AMD).

It is not clear why those who ate fish once a week had a slightly lower risk of early AMD, compared with those who ate fish three times a week, while the latter group enjoyed a much lower risk of late AMD. However, this is the kind of statistical anomaly that can occur in population studies, and the protective trend is clear.

The authors of the Aussie study (Chua B 2006) expressed a positive view of its implications: “A regular diet high in n-3 [omega-3] polyunsaturated fat, especially from fish, suggests protection against early and late ARM [age-related macular degeneration]....”

The Harvard affiliates study: omega-3/omega-6 balance seen keyIn the second study (Seddon JM 2006), researchers from the Massachusetts Eye and Ear Infirmary and Channing Laboratory—both affiliated with Harvard Medical School—studied the effects of smoking and fish consumption in elderly twins recruited from the National Research Council’s World War II Veteran Twin Registry. Of the 681 twins who participated in the study, 222 had been diagnosed with AMD and 459 twins had no signs of AMD.

The Boston-area team found that the risk of AMD was 45 percent lower among those who ate fish at least twice a week, compared with those who reported eating less than one serving of fish per week. (The current smokers among the twins had nearly twice the risk of developing AMD and past smokers were only slightly better off for having quit the habit.)

Unsurprisingly, the balance between omega-3 and omega-6 fatty acids played a key role in a twin’s risk of developing AMD. The authors reported that the reduction in risk seen among participants who consumed the highest levels of omega-3s occurred primarily among those who also ingested the least amounts of pro-inflammatory omega-6 fatty acids.

This highly significant finding supports the hypothesis—which is backed by a preponderance of evidence from heart disease and cancer studies—that omega-3s only deliver their optimal health benefits among people who consume much lower levels of omega-6 fatty acids than are standard in America and other developed countries.

The 10- to 50-fold excess of omega-6 fatty acids found in most Americans’ diets come mostly from grains, seeds, and the vegetable oils used most commonly in processed and prepared foods and for home and restaurant cooking (soy, corn, cottonseed, canola, safflower, sunflower).

What is AMD?Age-related macular degeneration begins when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye. This stage of AMD is called “early” or “dry” AMD.

As “dry” AMD progresses, three things happen: a blurred spot often appears in the field of vision, it becomes more difficult to recognize faces, and victims need more light for reading. While AMD generally affects both eyes, vision can be lost in one eye while the other eye seems unaffected.

The “late” stage of AMD referenced in our summary of the Australian study can include both the "dry" and "wet" forms. The “wet” form begins when abnormal blood vessels behind the retina start to grow under the macula and leak blood and fluid. These events raise the macula from its normal place at the back of the eye, causing a loss of central vision that can occur quickly.

An early symptom of wet AMD is that straight lines appear wavy. If you notice this condition or other changes to your vision, contact an eye doctor (ophthamologist) immediately.Could salmon be the best fish for curbing AMD?The results of recent animal research indicate that salmon may offer an eye-defending edge over other fish rich in omega-3s.

How spinach, broccoli, and company protect eyes from AMDLutein and zeaxanthin are key constituents of a spot in the central region of the retina known as the macula lutea, or “yellow spot”, which is vital to activities like reading and driving.

Because they are antioxidants as well as pigments, lutein and zeaxanthin probably help protect people from AMD by preventing retinal damage induced by free radicals (Chitchumroonchokchai C 2004).

Population studies indicate that people with the highest levels of lutein and zeaxanthin in their outer retina—thanks to diets rich in yellow-green vegetables—are far less likely to suffer from AMD, compared with those with the lowest levels.

However, only about half of the clinical trials using supplemental lutein and zeaxanthin have shown a clear risk reduction (Guymer RH 2006). It may be that the full range of constituents in selected yellow-green vegetables protects eyes better.

Wild salmon are the only commercial fish whose flesh is naturally rich in an unusually potent antioxidant called astaxanthin (as-tuh-zan-thin), which they get from the plankton (algae and minuscule larvae) and krill (tiny shrimp) in their diets. In addition to being a potent antioxidant, astaxanthin is a pigment that gives the flesh of wild salmon its characteristic red-orange hue.

(Note: Farmed salmon are fed synthetic astaxanthin to color their flesh orange. Since this molecule is structurally different from naturally occurring astaxanthin, it is unlikely to produce equivalent beneficial effects in the human body.)

So where does the astaxanthin in salmon fit into the AMD-prevention picture? Like lutein and zeaxanthin—see sidebar at right—astaxanthin belongs to the family of antioxidant pigments called xanthophylls (zan-thuh-fills).

Aside from astaxanthin’s strong structural similarities to lutein and zeaxanthin, and its proven antioxidant and anti-inflammatory effects in humans, the results of a recent study in rats suggest that it could be another ally against AMD.

When researchers administered astaxanthin to rats intravenously, it reduced inflammation—a key contributing factor in the development of AMD and cataracts—in the rodents’ eyes (Suzuki Y 2005). It remains to be seen whether dietary astaxanthin exerts a similar beneficial effect in people’s eyes, although that seems quite likely.

These preliminary findings suggest that salmon—more so than other fish rich in omega-3s—could be a potent ally in the battle to decelerate the aging process in our eyes.